Although the inhibition of normal ovarian cyclicity and ovulation that accompanies lactation is thought to result from the suppression of GnRH secretion, little is known about the neuronal systems in the hypothalamus that mediate the suppression of GnRH neuronal function. During lactation, the hypothalamus must integrate the effects of neural input arising from the suckling stimulus and of metabolic signals arising from the energy drain of milk production, which result in increased food intake. Thus, important systems to study would be those that have dual roles in the regulation of both reproductive function and food intake. The proposed studies will investigate two such systems, neuropeptide Y (NPY) and leptin. Using the lactating rat as a model, I will test the hypothesis that the changes in NPY and leptin shown to occur during lactation contribute to the inhibition of GnRH secretion. Data will be collected on physiological and neuroanatomical indices, such as LH and leptin secretion, and NPY and leptin receptor mRNA distribution. The use of antisense technology to block NPY action and administration of leptin will be employed to determine the relative contributions of each in the inhibition of GnRH/LH secretion. These studies will provide the first detailed characterization of changes in leptin and the leptin receptor during lactation and will determine whether changes in NPY and leptin play a causal role in the suppression of reproductive function during lactation.